EEG-MRI Study of the Effect of Methylphenidate on Neural Mechanisms in Adult Patients With ADHD With or Without Mood Disorders: a Randomized Controlled Trial Versus Placebo
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Adult ADHD
- Sponsor
- University Hospital, Strasbourg, France
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Effect of methylphenidate on the task vs. rest activation differential (treatment x group interaction) in a region defined by its involvement in the cognitive task and its responsiveness to methylphenidate.
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Attention Deficit Hyperactivity Disorder (ADHD) in adults is a common psychiatric disorder, with important consequences in terms of quality of life, mental health (associated disorders and poorer response to treatment), family life, risk of accidents; with a consequent cost for society.
Adult ADHD is frequently associated with psychiatric co-morbidities, and notably associated with mood disorders (major depressive disorder or bipolar disorder) in about 50% of cases.
The diagnosis of ADHD in adults is made in patients with an attentional complaint (pure ADHD or ADHD-P), but also very often in the management of a comorbid mood disorder (ADHD associated with mood disorder, or ADHD-MD). In this case, the ADHD had no impact during childhood and adolescence.
Medication management is well established for ADHD-P, and medication is based on methylphenidate, which has a rapid and significant effect on attentional symptoms and impulsivity. However, in the case of ADHD-HD, there is little evidence of treatment efficacy and the mechanisms of action of methylphenidate at the brain level are poorly understood.
The aim of the study is to determine the neural mechanisms of the effect of methylphenidate, using functional MRI and EEG, in ADHD-P and ADHD-HD patients, and to compare them to healthy subjects. A single dose allows us to observe effects that are then persistent with repeated doses. The aim is to determine, by means of a biomarker, whether methylphenidate treatment responds to the same mechanisms in the different groups and would be relevant in ADHD-P as in ADHD-HD.
Main objective:
To determine whether methylphenidate impacts differently on brain circuits associated with cognitive functions in the two clinical populations studied (adult ADHD patients and patients with post mood disorder attentional deficit) and in comparison to controls.
Secondary objectives:
- To determine the effect of methylphenidate on baseline brain flow in the two clinical populations and in controls (healthy subjects).
- To determine whether methylphenidate has a different impact on cognitive performance in the two clinical populations studied and in comparison to controls (healthy subjects).
- To confirm the effect of methylphenidate on the maintenance of cortical arousal.
- To distinguish the brain networks impacted by methylphenidate (maintenance of attention or inhibition) with MRI and EEG.
Detailed Description
It is a cross-over, randomized, controlled, double-blind, study. 3 groups of 20 subjects are constituted: A: adult patients with ADHD (ADHD-P) B: patients with attention deficit due to/emphasized by mood disorders (ADHD-HD) C: healthy control population During the inclusion visit the subjects fill in self-questionnaires (ASRS, WURS, WRAADDS, WFIRFS, TEMPS-A, BDI, BAI, RCTQ, mind-wandering). A 45-minute neuropsychological assessment will be carried out by a neuropsychologist, followed by training in the cognitive tasks used during the experimental sessions. During imaging session 1 (3 to 60 days from inclusion): Patients usually taking methylphenidate will discontinue methylphenidate treatment two days the imaging session. Subject takes treatment (or placebo) 30-60 minutes before MRI. The MRI is performed at rest and associated with cognitive tasks (SART) (65 minutes duration). EEG is performed after in combination with a cognitive task (SART) (duration 40 minutes). Finally subjects complete self-questionnaires. During imaging session 2 (14 to 90 days from inclusion): the same procedure is done again. Patients usually taking methylphenidate will discontinue methylphenidate treatment two days before the session. Subject takes placebo (if treatment during imaging session 1) or treatment (if placebo during imaging session 1) 30-60 minutes before MRI. MRI and EEG procedure are the same. fMRI imaging includes rest and imaging during SART task (Go-NoGo), using BOLD and ASL sequences. EEG is performed during SART task.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group A
Adult patients with ADHD (ADHD-P) receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)
Intervention: Placebo
Group A
Adult patients with ADHD (ADHD-P) receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)
Intervention: Methylphenidate immediate release 25mg
Group B
Adult patients with attention deficit due to/emphasized by mood disorders (ADHD-HD) receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)
Intervention: Placebo
Group B
Adult patients with attention deficit due to/emphasized by mood disorders (ADHD-HD) receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)
Intervention: Methylphenidate immediate release 25mg
Group C
Adult Healthy controls receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)
Intervention: Placebo
Group C
Adult Healthy controls receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)
Intervention: Methylphenidate immediate release 25mg
Outcomes
Primary Outcomes
Effect of methylphenidate on the task vs. rest activation differential (treatment x group interaction) in a region defined by its involvement in the cognitive task and its responsiveness to methylphenidate.
Time Frame: 2 hours after intake of methylphenidate or placebo
Changes in brain activations from J3-J600 to J14-J90 (MRI) in ADHD patients (ADHD-P and ADHD-HD), compared to healthy subjects(ADHD-P and ADHD-HD), compared to healthy subjects\] ROI (Region of Interest) analysis to maximize power.
Secondary Outcomes
- EEG spectrum power in the low frequencies (proportion of delta power (1-4Hz) and theta power EEG bands (4-8Hz)) in the methylphenidate vs. placebo condition(3 hours after intake of methylphenidate or placebo)
- MRI: Interaction group x treatment x task on brain activation related to sustained attention and inhibition corresponding to each of these tasks.(2 hours after intake of methylphenidate or placebo)
- Decrease in rCBF (regional Cerebral Blood Flow) in the methylphenidate vs. placebo condition, in the different groups (group x treatment interaction).(2 hours after intake of methylphenidate or placebo)
- EEG evoked potentials: Interaction group x treatment x task on the amplitude of the P300 wave related to sustained attention (P300b) and related to inhibition (P300a) corresponding to each of these tasks.(3 hours after intake of methylphenidate or placebo)
- Improved cognitive performance in sustained attention and inhibition tasks (SART : number of errors) following methylphenidate administration, in the different groups.(2 hours after intake of methylphenidate or placebo)